# Heat waves elevate risks of airway hypersensitivity that inhaled endogenous ions reduce

## TL;DR

Heat waves increase airway hypersensitivity risks, which can be reduced by inhaling alkaline aerosols containing endogenous ions.

## Contribution

A novel approach using alkaline aerosols of endogenous ions to reduce cough hypersensitivity during heat waves is proposed.

## Key findings

- Heat waves cause mucosal collapse and airway hypersensitivity, linked to gene expression changes like TRPV4 and CFTR.
- Inhaling alkaline (pH > 8) aerosols reduces cough bouts by 34% in chronic cough patients.
- Aerosols with pH < 8 had no significant effect on cough frequency.

## Abstract

Heat wave burden is rapidly rising relative to pre-industrial levels and exacerbating human respiratory illnesses. Yet, how to protect human airways, short of deep and sustained reductions in greenhouse gas emissions, remains unclear. Here, we find by climate modeling, continuum mechanics analysis, in vitro cell culture models, and human clinical data, that heat waves increase risks of cough hypersensitivity, which can be reduced by alkaline aerosols of endogenous salt ions. We predict that the mouth breathing of indoor and outdoor air during heat waves, by exposing human airways to aridity, causes mucosal collapse onto cilia and inflammatory compression of airway epithelial cells. Using airway lining interface cultures of human bronchial epithelial cells, we find that mucosal collapse alters the expression of genes associated with airway hypersensitivity, including TRPV4, PIEZO1, SCNN1A, SCNN1B, ANO1, and CFTR. Our theoretical and experimental models indicate that mucosal collapse can be reversed by inhalation of alkaline (pH > 8) hypertonic divalent salts for 4–6 hours by globular protein translocation toward the airway epithelium. We find, on analysis of cough recordings in a recently published clinical trial, that inhaling alkaline hypertonic divalent salt aerosols with pH > 8 every 4–6 hours significantly reduced placebo-adjusted cough bouts (34%) (n = 8) (p = 0.01) among refractory chronic cough patients. Inhaled aerosols of the same composition with pH < 8 had no effect on cough bouts (−12%) (n = 4). Aerosols with endogenous ions may help reduce global warming threats to human respiratory health.